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Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.

Publication ,  Journal Article
Gao, Y-J; Cheng, J-K; Zeng, Q; Xu, Z-Z; Decosterd, I; Xu, X; Ji, R-R
Published in: Exp Neurol
September 2009

Cancer pain significantly affects the quality of cancer patients, and current treatments for this pain are limited. C-Jun N-terminal kinase (JNK) has been implicated in tumor growth and neuropathic pain sensitization. We investigated the role of JNK in cancer pain and tumor growth in a skin cancer pain model. Injection of luciferase-transfected B16-Fluc melanoma cells into a hindpaw of mouse induced robust tumor growth, as indicated by increase in paw volume and fluorescence intensity. Pain hypersensitivity in this model developed rapidly (<5 days) and reached a peak in 2 weeks, and was characterized by mechanical allodynia and heat hyperalgesia. Tumor growth was associated with JNK activation in tumor mass, dorsal root ganglion (DRG), and spinal cord and a peripheral neuropathy, such as loss of nerve fibers in the hindpaw skin and induction of ATF-3 expression in DRG neurons. Repeated systemic injections of D-JNKI-1 (6 mg/kg, i.p.), a selective and cell-permeable peptide inhibitor of JNK, produced an accumulative inhibition of mechanical allodynia and heat hyperalgesia. A bolus spinal injection of D-JNKI-1 also inhibited mechanical allodynia. Further, JNK inhibition suppressed tumor growth in vivo and melanoma cell proliferation in vitro. In contrast, repeated injections of morphine (5 mg/kg), a commonly used analgesic for terminal cancer, produced analgesic tolerance after 1 day and did not inhibit tumor growth. Our data reveal a marked peripheral neuropathy in this skin cancer model and important roles of the JNK pathway in cancer pain development and tumor growth. JNK inhibitors such as D-JNKI-1 may be used to treat cancer pain.

Duke Scholars

Published In

Exp Neurol

DOI

EISSN

1090-2430

Publication Date

September 2009

Volume

219

Issue

1

Start / End Page

146 / 155

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Sensory Receptor Cells
  • Peripheral Nervous System Diseases
  • Peptides
  • Pain Measurement
  • Pain
  • Neurology & Neurosurgery
  • Morphine
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
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Gao, Y.-J., Cheng, J.-K., Zeng, Q., Xu, Z.-Z., Decosterd, I., Xu, X., & Ji, R.-R. (2009). Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model. Exp Neurol, 219(1), 146–155. https://doi.org/10.1016/j.expneurol.2009.05.006
Gao, Yong-Jing, Jen-Kun Cheng, Qing Zeng, Zhen-Zhong Xu, Isabelle Decosterd, Xiaoyin Xu, and Ru-Rong Ji. “Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.Exp Neurol 219, no. 1 (September 2009): 146–55. https://doi.org/10.1016/j.expneurol.2009.05.006.
Gao Y-J, Cheng J-K, Zeng Q, Xu Z-Z, Decosterd I, Xu X, et al. Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model. Exp Neurol. 2009 Sep;219(1):146–55.
Gao, Yong-Jing, et al. “Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.Exp Neurol, vol. 219, no. 1, Sept. 2009, pp. 146–55. Pubmed, doi:10.1016/j.expneurol.2009.05.006.
Gao Y-J, Cheng J-K, Zeng Q, Xu Z-Z, Decosterd I, Xu X, Ji R-R. Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model. Exp Neurol. 2009 Sep;219(1):146–155.
Journal cover image

Published In

Exp Neurol

DOI

EISSN

1090-2430

Publication Date

September 2009

Volume

219

Issue

1

Start / End Page

146 / 155

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Sensory Receptor Cells
  • Peripheral Nervous System Diseases
  • Peptides
  • Pain Measurement
  • Pain
  • Neurology & Neurosurgery
  • Morphine
  • Mice, Inbred C57BL
  • Mice